Delivering an API to a patient requires more than just identifying a molecule and its use. An API must be formulated for delivery to a patient and this formulation (in addition to the API activity) is evaluated by regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). The FDA evaluates the formulation for, among other properties, delivery properties, stability, consistency, and manufacturing controls. An important factor in determining the properties of a particular formulation is the form of the API. APIs have been known to exist as amorphous forms, crystalline forms, polymorphs, hydrates and solvates. The forms for every API are different. While one particular API may be known to exist as a polymorph or a solvate, another API may be known to only exist in amorphous form. This form diversity is important because each different polymorph, solvate, hydrate or amorphous form may have different properties such as stability, solubility, and hygroscopicity.
Some forms of an API can be formulated into an FDA approvable formulation, while other forms lack the required properties to meet the high regulatory standards of the FDA. Even if a particular API can exist in more than one form suitable for formulation, different properties of an API form can affect the manufacturing process, shelf stability, route of administration, bioavailability and other important product characteristics. For example, the ability to improve or modulate stability or hygroscopicity can decrease manufacturing costs by reducing the need for humidity controlled chambers or reducing the need to package an API in humidity resistant packaging. In addition these same changes can increase product shelf stability thereby improving product distribution possibilities and affecting cost. In another example, one form of an API may have greater bioavailability than another form. Choosing the higher bioavailability form allows for a lower drug dose to be administered to a patient.
Thus, increasing the form diversity of a particular API increases opportunities to identify the ideal form for formulation. In addition, increasing form diversity increases the possibility of finding improved forms which can reduce manufacturing costs, increase shelf stability, offer new routes of administration, and offer new formulation options.
(S)-(+)-2-(2-chlorophenyl)-2-hydroxy-ethyl carbamate is useful for treating disorders of the central nervous system and is currently in clinical trials for such disorders. (S)-(+)-2-(2-chlorophenyl)-2-hydroxy-ethyl carbamate and methods of making this molecule are disclosed in U.S. Pat. No. 6,103,759. Applicants have discovered that (S)-(+)-2-(2-chlorophenyl)-2-hydroxy-ethyl carbamate can form a novel crystal possessing a distinct physical properties and a distinct crystal structure different than previously known forms of (S)-(+)-2-(2-chlorophenyl)-2-hydroxy-ethyl carbamate. This discovery increases opportunities for the identification of an improved formulation suitable for FDA approval and for the ability of affect manufacturing process, shelf stability, route of administration, bioavailability and other product characteristics.